Gold Nanoparticles in Surface Plasmon Resonance

Surface Plasmon Resonance (SPR) technology has long been a cornerstone in biosensing, chemical analysis, and material science due to its ability to detect molecular interactions in real time without labels.

However, as the demand for higher sensitivity and performance grows, traditional SPR systems face limitations in detecting low-concentration molecules and maintaining stability in complex environments.

SPR technology is like a high-precision microscope capable of observing molecular interactions, but in some cases, its "vision" may not be sharp enough to pick up faint signals. At this point, GNPs are like attaching a "super magnifying glass" to the microscope. With their unique LSPR effect, gold nanoparticles are able to magnify weak molecular signals several times, just like making a blurred image visible.

For example, gold nanoparticles can help SPR technology detect very low concentrations of tumor markers, like quickly finding the most critical person in a population. This "signal amplifier" enabled a qualitative leap in the sensitivity and performance of SPR technology, truly becoming a game-changing innovation.

By integrating GNPs into SPR systems, researchers have unlocked unprecedented levels of sensitivity, resolution, and reliability, paving the way for breakthroughs in healthcare, environmental monitoring, and beyond. This article explores the transformative role of gold nanoparticles in SPR, highlighting how they address key challenges and open new frontiers in science and technology.

The status and future of SPR technology

Since its introduction in the 1980s, surface plasmon resonance technology has become an important tool in biosensing, chemical analysis, and materials science. The core principle is to detect molecular interactions in real-time by monitoring plasmon resonance phenomena on metal surfaces (usually gold or silver). You can read the article A Comprehensive Guide to Biacore Instruments Features, Specifications, and Applications for more detailed knowledge.

SPR technology has been widely used in drug development, disease diagnosis, environmental monitoring, and other fields because of its advantages such as no label, high sensitivity, and real-time tracking. We also detailed examples in our previous article in Biacore Sensor Chips Types, Applications, and Selection Guide.

To address these challenges, scientists have turned to nanotechnology, especially gold nanoparticles. Gold nanoparticles are ideal materials for improving SPR performance due to their unique optical properties, high specific surface area, and biocompatibility. By combining gold nanoparticles with SPR technology, not only the detection sensitivity can be significantly enhanced, but also the application range can be expanded.

Science and Technology of Gold Nanoparticles

Traditional SPR technologies face issues such as insufficient sensitivity, low resolution, and poor stability in practical applications, while Gold Nanoparticles provide an effective solution to these pain points through their unique optical properties and physicochemical properties.

Increase Sensitivity

When light interacts with metal nanoparticles, the electric field of the light induces a collective oscillation of the conduction electrons at the nanoparticle surface. This oscillation is known as a surface plasmon. For nanoparticles, these plasmons are localized, meaning they are confined to the surface of the nanoparticle rather than propagating along a metal-dielectric interface.

The sensitivity of traditional SPR technology is limited by the attenuation length and signal strength of the electromagnetic field, and the detection ability of low-concentration molecules or small biomarkers is limited. Gold nanoparticles significantly enhance the intensity of the SPR signal through the local surface plasmon resonance effect. Its working principle can be divided into the following three parts:

• Electromagnetic field enhancement effect: When the incident light shines on the surface of gold nanoparticles, its free electrons will be excited to produce collective oscillation, forming a strong local electromagnetic field. This electromagnetic field is several times stronger than surface plasma waves in conventional SPR technology, amplifying the signal generated by the binding of the target molecule to the probe molecule.
• Signal amplification mechanism: Gold nanoparticles can act as "nanoantenna" that convert binding events of target molecules into stronger optical signals. For example, in biosensing, nanoparticle-modified SPR chips can amplify the binding signal of proteins or DNA by more than 10 times.
• Low-concentration detection capability: Through the signal enhancement effect of gold nanoparticles, SPR technology can detect low-concentration molecules at the picomolar or even femtomolar level, meeting the needs of high-sensitivity detection.

Improve Resolution

In complex samples (such as serum, and cell lysates), traditional SPR techniques can be disturbed by non-specific adsorption or background noise, resulting in decreased resolution and difficulty in distinguishing target molecules from other components. Gold nanoparticles can optimize the resolution of the SPR in a number of ways:

• Selective modification: The surface of gold nanoparticles can be chemically modified (such as sulfhydrylation, and amination) to bind to specific probe molecules (such as antibodies, and aptamers), so as to achieve highly selective detection of target molecules.
• Background noise suppression: The LSPR effect of gold nanoparticles is mainly concentrated near the surface of the nanoparticles, which reduces the interference of far-field noise, thus improving the signal-to-noise ratio of the signal.
• Improved spatial resolution: The size of gold nanoparticles is usually between 10-100 nanometers, and its local electromagnetic field effect can limit the detection area to the nanometer scale, thus improving the spatial resolution of the SPR.

Improve Stability

In traditional SPR systems, signal drift, baseline instability, or probe molecule inactivation may occur during long-term monitoring, which will affect the reliability and repeatability of detection results. Gold nanoparticles improve the stability of SPR systems in the following ways:

• Enhanced probe molecular stability: More probe molecules can be fixed on the surface of the gold nanoparticles, and through chemical bonding (such as gold-sulfur bonding) to ensure their firm adhesion, reducing the loss or inactivation of probe molecules.
• Anti-pollution ability: The surface of gold nanoparticles can be modified by hydrophilic molecules (such as polyethylene glycol, and PEG) to reduce non-specific adsorption, thereby improving the anti-pollution ability of the system.
• Long-term stability: Gold nanoparticles have good chemical stability and biocompatibility, and can maintain the same performance in complex environments for a long time. For example, in continuous monitoring experiments, the SPR chip modified with gold nanoparticles has a signal drift of less than 2% over 72 hours.

Preparation and Functionalization of Gold Nanoparticles

The preparation and functionalization of gold nanoparticles are the key to their successful application in SPR technology. At present, there are many ways to prepare gold nanoparticles, among which chemical reduction is one of the most common methods. The reduction of gold ions to gold atoms by a reducing agent (such as sodium citrate or sodium borohydride), and the formation of nanoparticles under the action of a stabilizer, this method is simple and inexpensive to operate, suitable for large-scale production.

In addition, the seed growth method can precisely control the size and shape of the particles by first preparing small gold nanoparticles as "seeds" and then controlling their growth process, for example, by preparing rod or star-shaped nanoparticles. For applications requiring high-purity gold nanoparticles, laser ablation is an ideal choice, which uses a high-energy laser to bombard the gold target and directly generate pure nanoparticles, avoiding the introduction of chemical reagents.

However, the prepared gold nanoparticles often need to be further functionalized to meet the needs of specific applications. Surface functionalization is the process of introducing specific functional groups or molecules on the surface of gold nanoparticles by chemical modification or physical adsorption.

For example, mercaptoylation uses the strong chemical bond between gold and sulfur to fix sulfhydryl compounds (such as mercaptoethylamine or mercaptopropionic acid) on the surface of gold nanoparticles, which is often used for surface modification of SPR chips to enhance their detection sensitivity. In addition, amination modification enables gold nanoparticles to further couple carboxylated molecules or prepare ph-responsive materials by introducing amino groups, which have a wide range of applications in drug delivery and biosensing.

To further improve the biocompatibility and stability of gold nanoparticles, polymer coating (such as polyethylene glycol PEG) is a common strategy that reduces non-specific adsorption and extends the cycle time of nanoparticles in living organisms.

Multi-field Application of Gold Nanoparticle-SPR

The combination of gold nanoparticles with surface plasmon resonance technology opens up new possibilities in many fields. By increasing sensitivity, resolution, and stability, GNP-SPR systems have become powerful tools for scientific research and industrial applications. Here are some key areas where the technology is making a big impact.

Life Sciences: Revolutionizing Biomedical Research and Diagnostics

GNP-SPR technology has proven to be a game-changer in the early diagnosis of diseases. Its high sensitivity allows for the detection of low-concentration biomarkers, such as proteins, nucleic acids, and exosomes, in complex biological samples.

A typical example is Gupta N et al., for cancer treatment through the properties of gold nanoparticles that strongly absorb near-infrared light. Gold nanoparticles that mediate photothermal therapy can warn cancer cells of chemotherapy, and regulate genes, and immunotherapy by enhancing cell permeability and intracellular delivery.

The process of necrosis and apoptosis depends on the power of the laser and the temperature within the cancer tissue achieved during irradiation. Cell death mechanisms are also important because cells that die through the necrotic process can support secondary tumor growth, while cells that die through apoptosis may trigger an immune response to inhibit the development of secondary tumor growth.

To reduce barriers in vivo, the gold nanostructures are again modified with targeting ligands and bioresponsive connectors. The manuscript concludes that the use of gold nanoparticles was able to inhibit the growth of cancer cells through the use of photothermal therapy, which has fewer side effects compared to other wire therapies.

Figure 1. Gold nanoparticles carry out the cancer treatment process. (Gupta N,2021)

Environmental Monitoring: Safeguarding Ecosystems

Due to the overuse of antibiotics in the world, bacterial infections have become a deadly threat. Based on their excellent chemical and physical properties, various gold (Au) based nanostructures have been widely explored as antimicrobials against bacterial infections. Many AU-based nanostructures have been designed and their antimicrobial activity and mechanisms have been further studied and demonstrated.

GNP-SPR technology can rapidly identify pathogenic microorganisms in environmental samples, such as bacteria and viruses, ensuring public health safety.

Anisotropic AuNRs have many antimicrobial applications due to their unique surface plasmon resonance. AuNR has two types of SPR absorption, including transverse and longitudinal surface plasma absorption. Based on their SPR, AUNRs can interact with incident light and convert light energy into heat energy for PTT.

A recent study reported the antimicrobial activity of AuNRs636 (longitudinal plasmon peak at 636 nm), AuNRs772 (longitudinal plasmon peak at 772 m), AuNPs, and AgNPs under incandescent light. In a typical study, Mutalik C et al. exploited the property that gold nanorods become efficient nanoconverters when irradiated by a resonant laser to effectively generate heat for PPTT applications. In this study, the goal was to evaluate the antimicrobial effects of easily synthesized, purified, and water-dispersed GNR on E. coli.

Figure 2. Preparation and antibacterial application of molybdenum disulfide conjugated gold nanorods nanocomposites. (Mutalik C,2023)

Food Safety: Ensuring Quality and Security

Food science researchers are generally concerned about the loss of food due to a shortened shelf life. As a result, the food industry seems most open to any technology that helps improve food packaging. It has been demonstrated that the use of nanotechnology-based technologies, such as metal-based nanoparticles, can remove unresolved barriers to reduced shelf life and environmental concerns.

With signs of major advances in nanoscience, there has been great interest in using gold nanoparticle methods based on green synthesis as the most advantageous metal compared to traditional chemic-based methods. Interestingly, due to the large surface volume ratio, the above method has great potential to simplify targeted drug delivery of gold nanoparticles, and with reduced biohazards, aims to improve stability and induce antimicrobial or antioxidant properties.

In their experimental study, Annamalai et al aimed to synthesize AuNPs from Euphorbia leaf extract and evaluate its biological (antimicrobial) activity. They recruited surface plasmon resonance to characterize and confirm the synthesized AuNP by changing the extract's color from pale yellow to purple (nanoparticles ranging in size from 6 nm to 71 nm).